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1.
Cancer Causes Control ; 30(10): 1113-1126, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31392546

RESUMO

PURPOSE: We examined associations of inflammation with breast density, a marker of breast cancer risk, among female Chinese immigrants and explored whether associations varied by neighborhood environment. METHODS: Assessments of serum C-reactive protein (CRP), soluble tumor necrosis factor receptor 2 (sTNFR2), and breast density were performed among 401 Chinese immigrants across the Philadelphia region. Participant addresses were geocoded, with the majority residing in areas representing traditional urban enclaves (i.e., Chinatown and South Philadelphia) or an emerging enclave with a smaller, but rapidly growing Chinese immigrant population (i.e., the Near Northeast). The remainder was classified as residing in non-enclaves. RESULTS: In multivariable adjusted regression models, CRP was inversely associated with dense breast area (p = 0.01). Levels of sTNFR2 were also inversely associated with dense breast area, but these associations varied by neighborhood (interaction p = 0.01); specifically, inverse associations were observed among women residing in the emerging enclave (p = 0.03), but not other neighborhoods. CONCLUSIONS: Among Chinese immigrant women, aggregate analyses that do not take neighborhood context into consideration can mask potential variations in association of inflammatory markers with breast density. Future studies should consider how neighborhood contextual factors may contribute to differential risk pathways.

2.
Mol Genet Genomic Med ; 7(9): e898, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31376244

RESUMO

BACKGROUND: While there is increasing interest in sharing genetic research results with participants, how best to communicate the risks, benefits and limitations of research results remains unclear. METHODS: Participants who received genetic research results answered open and closed-ended questions about their experiences receiving results and interest in and advantages and disadvantages of a web-based alternative to genetic counseling. RESULTS: 107 BRCA1/2 negative women with a personal or family history of breast cancer consented to receive genetic research results and 82% completed survey items about their experience. Most participants reported there was nothing they disliked (74%) or would change (85%) about their predisclosure or disclosure session (78% and 89%). They most frequently reported liking the genetic counselor and learning new information. Only 24% and 26% would not be willing to complete predisclosure counseling or disclosure of results by a web-based alternative, respectively. The most frequently reported advantages included convenience and reduced time. Disadvantages included not being able to ask questions, the risk of misunderstanding and the impersonal nature of the encounter. CONCLUSION: Most participants receiving genetic research results report high satisfaction with telephone genetic counseling, but some may be willing to consider self-directed web alternatives for both predisclosure genetic education and return of results.

3.
Med Care ; 57(9): 728-733, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31313685

RESUMO

BACKGROUND: Regionalization to higher volume centers has been proposed as a mechanism to improve short-term outcomes following complex surgery. OBJECTIVE: The objective of this study was to assess trends in regionalization and mortality for patients undergoing radical cystectomy (RC). RESEARCH DESIGN: An observational study of patients receiving RC in the United States from 2004 to 2013. SUBJECTS: Data for patients receiving RC were extracted from the National Cancer Database. MEASURES: The primary exposure was hospital volume; low-volume hospitals (LVH) included those with <5 RC/year and high-volume hospitals (HVH) were those with ≥30 RC/year. Trends in the volume were assessed, as were 30- and 90-day mortality. Cochrane-Armitage tests were performed for volume, and propensity score-weighted proportional hazard regression was used to assess mortality. RESULTS: A total of 47,028 RC were performed in 1162 hospitals from 2004 to 2013. The proportion of RC at LVH declined from 29% to 17% (P<0.01), whereas that of HVH increased from 16% to 33% (P<0.01). Unadjusted 30- (P=0.02) and 90-day (P<0.001) mortality decreased, and the absolute decrease was greatest at LVH (4.8% vs. 2.6%, P=0.03), whereas rates for HVH remained stable (1.9% vs. 1.4%, P=0.34). Following risk-adjustment, relative to treatment at HVH, treatment at LVH was associated with increased 30-day (hazard ratio: 1.66, 95% CI: 1.53-1.80) and 90-day mortality (hazard ratio: 1.37, 95% confidence interval: 1.30-1.44). CONCLUSIONS: Regionalization of RC to HVH was observed from 2004 to 2013. Treatment at LVH was associated with 66% and 33% relative increases in hazard of death at 30 and 90 days, respectively. These findings support the selective referral of complex cases to higher volume centers.

4.
BJU Int ; 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31145523

RESUMO

OBJECTIVES: To develop a clinically applicable predictive model to quantitate the risk of estimated glomerular filtration rate (eGFR) decline to ≤45 mL/min/1.73 m2 after radical nephrectomy (RN) to better inform decisions between RN and partial nephrectomy (PN). PATIENTS AND METHODS: Our prospectively maintained kidney cancer registry was reviewed for patients with a preoperative eGFR >60 mL/min/1.73 m2 who underwent RN for a localized renal mass. New baseline renal function was indexed. We used multivariable logistic regression to develop a predictive nomogram and evaluated it using receiver-operating characteristic (ROC) analysis. Decision-curve analysis was used to assess the net clinical benefit. RESULTS: A total of 668 patients met the inclusion criteria, of whom 183 (27%) experienced a decline in eGFR to ≤45 mL/min/1.73 m2 . On multivariable analysis, increasing age (P = 0.001), female gender (P < 0.001), and increasing preoperative creatinine level (P < 0.001) were associated with functional decline. We constructed a predictive nomogram that included these variables in addition to comorbidities with a known association with kidney disease, but found that a simplified model excluding comorbidities was equally robust (cross-validated area under the ROC curve was 0.78). Decision-curve analysis showed the net clinical benefit at probabilities >~11%. CONCLUSIONS: The decision to perform RN vs PN is multifaceted. We have provided a simple quantitative tool to help identify patients at risk of a postoperative eGFR of ≤45 mL/min/1.73 m2 , who may be stronger candidates for nephron preservation.

5.
Otolaryngol Head Neck Surg ; 161(2): 245-250, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30939098

RESUMO

OBJECTIVE: To highlight common pitfalls observed in scientific research derived from national cancer registries, predominantly the Survival, Epidemiology, and End Results Program and the National Cancer Database. DATA SOURCES: Literature review and expert opinion. REVIEW METHODS: This state-of-the-art review consolidates the literature with editorial experiences describing how and why statistically flawed studies are usually rejected for publication, highlighting common errors in submitted articles employing national cancer registries. CONCLUSIONS: Pitfalls were identified in 2 major areas-design and data analysis. Design pitfalls included unbalanced cohorts, uncontrolled covariates, and flawed oncologic variables. Analytical pitfalls included incorrect application of univariate analyses, inclusion of inaccurate data, and inclusion of stage IVc disease in curative survival analysis. Additional limitations of database studies were identified, including absence of patient-related outcomes, hypothesis-generating vs practice-changing implications, and inability to differentiate between overall survival and disease-specific survival. IMPLICATIONS FOR PRACTICE: Methodological strategies are suggested to ensure careful analytical design and appropriate interpretation. Although national cancer registries provide a wealth of data, researchers must remain vigilant when designing studies and analyzing these data sets. Inherent design flaws raise considerable problems with interpretation; however, when analyzed judiciously, registries can lead to a better understanding of cancer outcomes.

6.
BMC Med Inform Decis Mak ; 18(Suppl 4): 123, 2018 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-30537974

RESUMO

BACKGROUND: There has been an increasing interest in learning low-dimensional vector representations of medical concepts from Electronic Health Records (EHRs). Vector representations of medical concepts facilitate exploratory analysis and predictive modeling of EHR data to gain insights about the patterns of care and health outcomes. EHRs contain structured data such as diagnostic codes and laboratory tests, as well as unstructured free text data in form of clinical notes, which provide more detail about condition and treatment of patients. METHODS: In this work, we propose a method that jointly learns vector representations of medical concepts and words. This is achieved by a novel learning scheme based on the word2vec model. Our model learns those relationships by integrating clinical notes and sets of accompanying medical codes and by defining joint contexts for each observed word and medical code. RESULTS: In our experiments, we learned joint representations using MIMIC-III data. Using the learned representations of words and medical codes, we evaluated phenotypes for 6 diseases discovered by our and baseline method. The experimental results show that for each of the 6 diseases our method finds highly relevant words. We also show that our representations can be very useful when predicting the reason for the next visit. CONCLUSIONS: The jointly learned representations of medical concepts and words capture not only similarity between codes or words themselves, but also similarity between codes and words. They can be used to extract phenotypes of different diseases. The representations learned by the joint model are also useful for construction of patient features.


Assuntos
Registros Eletrônicos de Saúde , Aprendizado de Máquina , Processamento de Linguagem Natural , Codificação Clínica , Humanos , Fenótipo , Terminologia como Assunto , Vocabulário
7.
Clin Genet ; 2018 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-30417332

RESUMO

Telephone disclosure of cancer genetic test results is noninferior to in-person disclosure. However, how patients who prefer in-person communication of results differ from those who agree to telephone disclosure is unclear but important when considering delivery models for genetic medicine. Patients undergoing cancer genetic testing were recruited to a multicenter, randomized, noninferiority trial (NCT01736345) comparing telephone to in-person disclosure of genetic test results. We evaluated preferences for in-person disclosure, factors associated with this preference and outcomes compared to those who agreed to randomization. Among 1178 enrolled patients, 208 (18%) declined randomization, largely given a preference for in-person disclosure. These patients were more likely to be older (P = 0.007) and to have had multigene panel testing (P < 0.001). General anxiety (P = 0.007), state anxiety (P = 0.008), depression (P = 0.011), cancer-specific distress (P = 0.021) and uncertainty (P = 0.03) were higher after pretest counseling. After disclosure of results, they also had higher general anxiety (P = 0.003), depression (P = 0.002) and cancer-specific distress (P = 0.043). While telephone disclosure is a reasonable alternative to in-person disclosure in most patients, some patients have a strong preference for in-person communication. Patient age, distress and complexity of testing are important factors to consider and requests for in-person disclosure should be honored when possible.

8.
Contemp Clin Trials Commun ; 9: 135-142, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29696236

RESUMO

Background: Increasing diversity in clinical trials may be worthwhile. We examined clinical trials that restricted eligibility to a single race or ethnicity. Methods: We reviewed 19,246 trials registered on ClinicalTrials.gov through January 2013. We mapped trial ZIP-codes to U.S. Census and American Community Survey data. The outcome was whether trials required participants to be from a single racial or ethnic group. Results: In adjusted analyses, the odds of trials restricting eligibility to a single race/ethnicity increased by 4% per year (95% CI 1.01-1.08, p = .024). Behavioral (5.79% with single race/ethnicity requirements), skin-related (4.49%), and Vitamin D (6.14%) studies had higher rates of single race/ethnicity requirements. Many other trial-specific characteristics, such as funding agency and region of the U.S. in which the trial opened, were associated with eligibility restrictions. In terms of neighborhood characteristics, studies with single race eligibility requirements were more likely to be located in ZIP-codes with greater percentages of those self-reporting the characteristic. For example, 35.2% (SD = 24.9%) of the population self-reported themselves as Black or African American in ZIP-codes with trials requiring participants to be Black/African American, but only 5.9% (SD = 6.9%) self-reported themselves as Black/African American in ZIP-codes with trials that required Asian ethnicity. In ZIP-codes with trials requiring Asian ethnicity, 24.6% (SD = 16.2%) self-reported as Asian. In ZIP-codes with trials requiring Hispanic/Latino ethnicity, 33.3% (SD = 28.5%) self-reported as Hispanic/Latino. Neighborhood level poverty rates and reduced English language ability were also associated with more single race eligibility requirements. Conclusions: In selected fields, there has been a modest temporal increase in single race/ethnicity inclusion requirements. Some studies may not fall under regulatory purview and hence may be less likely to include diverse samples. Conversely, some eligibility requirements may be related to health disparities research. Future work should examine whether targeted enrollment criteria facilitates development of personalized medicine or reduces trial access.

9.
J Natl Cancer Inst ; 110(9): 985-993, 2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-29490071

RESUMO

Background: Germline genetic testing is standard practice in oncology. Outcomes of telephone disclosure of a wide range of cancer genetic test results, including multigene panel testing (MGPT) are unknown. Methods: Patients undergoing cancer genetic testing were recruited to a multicenter, randomized, noninferiority trial (NCT01736345) comparing telephone disclosure (TD) of genetic test results with usual care, in-person disclosure (IPD) after tiered-binned in-person pretest counseling. Primary noninferiority outcomes included change in knowledge, state anxiety, and general anxiety. Secondary outcomes included cancer-specific distress, depression, uncertainty, satisfaction, and screening and risk-reducing surgery intentions. To declare noninferiority, we calculated the 98.3% one-sided confidence interval of the standardized effect; t tests were used for secondary subgroup analyses. Only noninferiority tests were one-sided, others were two-sided. Results: A total of 1178 patients enrolled in the study. Two hundred eight (17.7%) participants declined random assignment due to a preference for in-person disclosure; 473 participants were randomly assigned to TD and 497 to IPD; 291 (30.0%) had MGPT. TD was noninferior to IPD for general and state anxiety and all secondary outcomes immediately postdisclosure. TD did not meet the noninferiority threshold for knowledge in the primary analysis, but it did meet the threshold in the multiple imputation analysis. In secondary analyses, there were no statistically significant differences between arms in screening and risk-reducing surgery intentions, and no statistically significant differences in outcomes by arm among those who had MGPT. In subgroup analyses, patients with a positive result had statistically significantly greater decreases in general anxiety with telephone disclosure (TD -0.37 vs IPD +0.87, P = .02). Conclusions: Even in the era of multigene panel testing, these data suggest that telephone disclosure of cancer genetic test results is as an alternative to in-person disclosure for interested patients after in-person pretest counseling with a genetic counselor.

10.
Clin Cancer Res ; 24(6): 1375-1388, 2018 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-29437795

RESUMO

Purpose: The role of cholesterol biosynthesis in hedgehog pathway activity and progression of hedgehog pathway medulloblastoma (Hh-MB) were examined in vivo Statins, commonly used cholesterol-lowering agents, were utilized to validate cholesterol biosynthesis as a therapeutic target for Hh-MB.Experimental Design: Bioinformatic analysis was performed to evaluate the association between cholesterol biosynthesis with hedgehog group medulloblastoma in human biospecimens. Alterations in hedgehog signaling were evaluated in medulloblastoma cells after inhibition of cholesterol biosynthesis. The progression of endogenous medulloblastoma in mice was examined after genetic blockage of cholesterol biosynthesis in tumor cells. Statins alone, or in combination with vismodegib (an FDA-approved Smoothened antagonist), were utilized to inhibit medulloblastoma growth in vivoResults: Cholesterol biosynthesis was markedly enhanced in Hh-MB from both humans and mice. Inhibition of cholesterol biosynthesis dramatically decreased Hh pathway activity and reduced proliferation of medulloblastoma cells. Statins effectively inhibited medulloblastoma growth in vivo and functioned synergistically in combination with vismodegib.Conclusions: Cholesterol biosynthesis is required for Smoothened activity in the hedgehog pathway, and it is indispensable for the growth of Hh-MB. Targeting cholesterol biosynthesis represents a promising strategy for treatment of Hh-MB. Clin Cancer Res; 24(6); 1375-88. ©2018 AACR.

11.
Int J Cancer ; 142(2): 262-270, 2018 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-28921520

RESUMO

Animal and experimental data suggest that anti-Müllerian hormone (AMH) serves as a marker of ovarian reserve and inhibits the growth of ovarian tumors. However, few epidemiologic studies have examined the association between AMH and ovarian cancer risk. We conducted a nested case-control study of 302 ovarian cancer cases and 336 matched controls from nine cohorts. Prediagnostic blood samples of premenopausal women were assayed for AMH using a picoAMH enzyme-linked immunosorbent assay. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariable-adjusted conditional logistic regression. AMH concentration was not associated with overall ovarian cancer risk. The multivariable-adjusted OR (95% CI), comparing the highest to the lowest quartile of AMH, was 0.99 (0.59-1.67) (Ptrend : 0.91). The association did not differ by age at blood draw or oral contraceptive use (all Pheterogeneity : ≥0.26). There also was no evidence for heterogeneity of risk for tumors defined by histologic developmental pathway, stage, and grade, and by age at diagnosis and time between blood draw and diagnosis (all Pheterogeneity : ≥0.39). In conclusion, this analysis of mostly late premenopausal women from nine cohorts does not support the hypothesized inverse association between prediagnostic circulating levels of AMH and risk of ovarian cancer.


Assuntos
Adenocarcinoma de Células Claras/etiologia , Adenocarcinoma Mucinoso/etiologia , Biomarcadores/sangue , Cistadenocarcinoma Seroso/etiologia , Neoplasias do Endométrio/etiologia , Neoplasias Ovarianas/etiologia , Adenocarcinoma de Células Claras/sangue , Adenocarcinoma de Células Claras/epidemiologia , Adenocarcinoma Mucinoso/sangue , Adenocarcinoma Mucinoso/epidemiologia , Adulto , Hormônio Antimülleriano/sangue , Estudos de Casos e Controles , Estudos de Coortes , Cistadenocarcinoma Seroso/sangue , Cistadenocarcinoma Seroso/epidemiologia , Neoplasias do Endométrio/sangue , Neoplasias do Endométrio/epidemiologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/epidemiologia , Pré-Menopausa , Prognóstico , Adulto Jovem
12.
Ann Surg ; 267(4): 734-742, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28151800

RESUMO

OBJECTIVE: The objective of this study was to determine the relationship between bowel preparation and surgical site infections (SSIs), and also other postoperative complications, after elective colorectal surgery. BACKGROUND: SSI is a major source of postoperative morbidity/costs after colorectal surgery. The value of preoperative bowel preparation to prevent SSI remains controversial. METHODS: We analyzed 32,359 patients who underwent elective colorectal resections in the American College of Surgeons National Surgery Quality Improvement Program database from 2012 to 2014. Univariable and multivariable analyses were performed; propensity adjustment using patient/procedure characteristics was used to account for nonrandom receipt of bowel preparation. RESULTS: 26.7%, 36.6%, 3.8%, and 32.9% of patients received no bowel preparation, mechanical bowel preparation (MBP), oral antibiotics (OA), and MBP + OA, respectively. After propensity adjustment, MBP was not associated with decreased risk of SSI compared with no bowel preparation. In contrast, both OA and OA + MBP were associated with decreased risk of any SSI (adjusted odds ratio 0.49, 95% confidence interval 0.38-0.64; and adjusted odds ratio 0.45, 95% confidence interval 0.40-0.50, respectively) compared with no bowel preparation. OA and MBP + OA were associated with decreased risks of anastomotic leak, postoperative ileus, readmission, and also shorter length of stay (all P < 0.05). Bowel preparation was not associated with increased risk of cardiac/renal complications compared with no preparation. CONCLUSIONS: The use of MBP alone before elective colorectal resection to prevent SSI is ineffective and should be abandoned. In contrast, OA and MBP + OA are associated with decreased risks of SSI and are not associated with increased risks of other adverse outcomes compared with no preparation. Prospective studies to determine the efficacy of OA are warranted; in the interim, MBP + OA should be used routinely before elective colorectal resection to prevent SSI.

13.
Health Serv Outcomes Res Methodol ; 17(3-4): 237-255, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29176931

RESUMO

Prognostic scores have been proposed as outcome based confounder adjustment scores akin to propensity scores. However, prognostic scores have not been widely used in the substantive literature. Instead, comorbidity scores, which are limited versions of prognostic scores, have been used extensively by clinical and health services researchers. A comorbidity is an existing disease an individual has in addition to a primary condition of interest, such as cancer. Comorbidity scores are used to reduce the dimension of a vector of comorbidity variables into a single scalar variable. Such scores are often added to regression models with other non-comorbidity variables such as age and sex, both for analyzing prognosis and for confounder adjustment when analyzing treatment effects. Despite their widespread use, the properties of and conditions under which comorbidity scores are valid dimension reduction tools in statistical models is largely unknown. In this article, we show that under relatively standard assumptions, comorbidity scores can have equal prognostic and confounder-adjustment abilities as the individual comorbidity variables, but that biases can occur if there are additional effects, such as interactions, of covariates beyond that captured by the comorbidity score. Simulations were performed to illustrate empirical properties and a data example using breast cancer data from the SEER Medicare Database demonstrates the application of these results.

14.
J Am Stat Assoc ; 112(518): 534-546, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28966417

RESUMO

Rates of kidney cancer have been increasing, with small incidental tumors experiencing the fastest growth rates. Much of the increase could be due to increased use of CT scans, MRIs, and ultrasounds for unrelated conditions. Many tumors might never have been detected or become symptomatic in the past. This suggests that many patients might benefit from less aggressive therapy, such as active surveillance by which tumors are surgically removed only if they become sufficiently large. However, it has been difficult for clinicians to identify subgroups of patients for whom treatment might be especially beneficial or harmful. In this work, we use a principal stratification framework to estimate the proportion and characteristics of individuals who have large or small hazard rates of death in two treatment arms. This allows us to assess who might be helped or harmed by aggressive treatment. We also use Weibull mixture models. This work differs from much previous work in that the survival classes upon which principal stratification is based are latent variables. That is, survival class is not an observed variable. We apply this work using Surveillance Epidemiology and End Results-Medicare claims data. Clinicians can use our methods for investigating treatments with heterogeneous effects.

15.
J Natl Compr Canc Netw ; 15(10): 1224-1233, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28982748

RESUMO

Background: Although financial distress is commonly recognized in patients with cancer, it may be more prevalent in younger adults. This study sought to evaluate disparities in overall and financial distress in patients with cancer as a function of age. Methods: This was a single-center cross-sectional study of patients with solid malignancies requiring cancer therapy. The patient questionnaire included demographics, financial concerns, and measures of overall and financial distress. Data analyses compared patients in 3 age groups: young (<50 years), middle-aged (50-64 years), and elderly (≥65 years). Results: The cohort included 119 patients (median age, 62 years; 52% female; 84% white; 100% insured; 36% income ≥$75,000). Significant financial concerns included paying rent/mortgage (P=.003) and buying food (P=.032). Impact of Event Scale (IES) results revealed significant distress in 73% young, 64% middle-aged, and 44% elderly patients. The mean Distress Thermometer (DT) score was 6.1 (standard deviation [SD], 2.9) for young patients, 5.4 (SD, 2.6) for middle-aged, and 4.4 (SD, 3.3) for elderly patients. Young patients were more likely than elderly patients to have a higher IES distress score (P=.016) and DT score (P=.048). The mean InCharge score was lowest (indicating greatest financial distress) in the young group and progressed with age: 5.0 (SD, 1.9), 5.7 (SD, 2.7), and 7.4 (SD, 1.9), respectively (P<.001). Multivariable analyses revealed that the relationship between financial distress and overall distress was strongest in the middle-age group; as the DT increased by 1 point, the InCharge scores decreased by 0.52 (P<.001). Conclusions: Overall and financial distress are more common in young and middle-aged patients with cancer. There are several factors, including employment, insurance, access to paid sick leave, children, and education, that affect younger and middle-aged adults and are less of a potential stressor for elderly individuals.


Assuntos
Neoplasias/epidemiologia , Neoplasias/psicologia , Estresse Psicológico , Adulto , Fatores Etários , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Socioeconômicos , Adulto Jovem
16.
Br J Cancer ; 117(9): 1412-1418, 2017 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-28873086

RESUMO

BACKGROUND: The Mullerian ducts are the embryological precursors of the female reproductive tract, including the uterus; anti-Mullerian hormone (AMH) has a key role in the regulation of foetal sexual differentiation. Anti-Mullerian hormone inhibits endometrial tumour growth in experimental models by stimulating apoptosis and cell cycle arrest. To date, there are no prospective epidemiologic data on circulating AMH and endometrial cancer risk. METHODS: We investigated this association among women premenopausal at blood collection in a multicohort study including participants from eight studies located in the United States, Europe, and China. We identified 329 endometrial cancer cases and 339 matched controls. Anti-Mullerian hormone concentrations in blood were quantified using an enzyme-linked immunosorbent assay. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) across tertiles and for a doubling of AMH concentrations (ORlog2). Subgroup analyses were performed by ages at blood donation and diagnosis, oral contraceptive use, and tumour characteristics. RESULTS: Anti-Mullerian hormone was not associated with the risk of endometrial cancer overall (ORlog2: 1.07 (0.99-1.17)), or with any of the examined subgroups. CONCLUSIONS: Although experimental models implicate AMH in endometrial cancer growth inhibition, our findings do not support a role for circulating AMH in the aetiology of endometrial cancer.


Assuntos
Adenocarcinoma/sangue , Hormônio Antimülleriano/sangue , Biomarcadores Tumorais/sangue , Neoplasias do Endométrio/sangue , Adenocarcinoma/epidemiologia , Adenocarcinoma/patologia , Adulto , Estudos de Casos e Controles , China/epidemiologia , Neoplasias do Endométrio/epidemiologia , Neoplasias do Endométrio/patologia , Europa (Continente)/epidemiologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Estados Unidos/epidemiologia
17.
Policy Polit Nurs Pract ; 18(2): 72-83, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28735567

RESUMO

Providing affordable, high-quality care for the 10 million persons who are dual-eligible beneficiaries of Medicare and Medicaid is an ongoing health-care policy challenge in the United States. However, the workforce and the care provided to dual-eligible beneficiaries are understudied. The purpose of this article is to provide a narrative of the challenges and lessons learned from an exploratory study in the use of clinical and administrative data to compare the workforce of two care models that deliver home- and community-based services to dual-eligible beneficiaries. The research challenges that the study team encountered were as follows: (a) comparing different care models, (b) standardizing data across care models, and (c) comparing patterns of health-care utilization. The methods used to meet these challenges included expert opinion to classify data and summative content analysis to compare and count data. Using descriptive statistics, a summary comparison of the two care models suggested that the coordinated care model workforce provided significantly greater hours of care per recipient than the integrated care model workforce. This likely represented the coordinated care model's focus on providing in-home services for one recipient, whereas the integrated care model focused on providing services in a day center with group activities. The lesson learned from this exploratory study is the need for standardized quality measures across home- and community-based services agencies to determine the workforce that best meets the needs of dual-eligible beneficiaries.


Assuntos
Definição da Elegibilidade/legislação & jurisprudência , Política de Saúde , Necessidades e Demandas de Serviços de Saúde/legislação & jurisprudência , Cobertura do Seguro/legislação & jurisprudência , Medicaid/legislação & jurisprudência , Medicare/legislação & jurisprudência , Gastos em Saúde/legislação & jurisprudência , Acesso aos Serviços de Saúde/legislação & jurisprudência , Humanos , Estados Unidos
18.
Fertil Steril ; 107(4): 1012-1022.e2, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28366409

RESUMO

OBJECTIVE: To identify reproductive, lifestyle, hormonal, and other correlates of circulating antimüllerian hormone (AMH) concentrations in mostly late premenopausal women. DESIGN: Cross-sectional study. SETTING: Not applicable. PATIENT(S): A total of 671 premenopausal women not known to have cancer. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Concentrations of AMH were measured in a single laboratory using the picoAMH ELISA. Multivariable-adjusted median (and interquartile range) AMH concentrations were calculated using quantile regression for several potential correlates. RESULT(S): Older women had significantly lower AMH concentrations (≥40 [n = 444] vs. <35 years [n = 64], multivariable-adjusted median 0.73 ng/mL vs. 2.52 ng/mL). Concentrations of AMH were also significantly lower among women with earlier age at menarche (<12 [n = 96] vs. ≥14 years [n = 200]: 0.90 ng/mL vs. 1.12 ng/mL) and among current users of oral contraceptives (n = 27) compared with never or former users (n = 468) (0.36 ng/mL vs. 1.15 ng/mL). Race, body mass index, education, height, smoking status, parity, and menstrual cycle phase were not significantly associated with AMH concentrations. There were no significant associations between AMH concentrations and androgen or sex hormone-binding globulin concentrations or with factors related to blood collection (e.g., sample type, time, season, and year of blood collection). CONCLUSION(S): Among premenopausal women, lower AMH concentrations are associated with older age, a younger age at menarche, and currently using oral contraceptives, suggesting these factors are related to a lower number or decreased secretory activity of ovarian follicles.


Assuntos
Hormônio Antimülleriano/sangue , Estilo de Vida , Reserva Ovariana , Pré-Menopausa/sangue , Adulto , Fatores Etários , Ásia , Biomarcadores/sangue , Anticoncepcionais Orais Hormonais/uso terapêutico , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Europa (Continente) , Feminino , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Estudos Prospectivos , Globulina de Ligação a Hormônio Sexual/análise , Congêneres da Testosterona/sangue , Estados Unidos , Adulto Jovem
19.
Elife ; 62017 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-28139197

RESUMO

Desmoplasia, a fibrotic mass including cancer-associated fibroblasts (CAFs) and self-sustaining extracellular matrix (D-ECM), is a puzzling feature of pancreatic ductal adenocarcinoma (PDACs). Conflicting studies have identified tumor-restricting and tumor-promoting roles of PDAC-associated desmoplasia, suggesting that individual CAF/D-ECM protein constituents have distinguishable tumorigenic and tumor-repressive functions. Using 3D culture of normal pancreatic versus PDAC-associated human fibroblasts, we identified a CAF/D-ECM phenotype that correlates with improved patient outcomes, and that includes CAFs enriched in plasma membrane-localized, active α5ß1-integrin. Mechanistically, we established that TGFß is required for D-ECM production but dispensable for D-ECM-induced naïve fibroblast-to-CAF activation, which depends on αvß5-integrin redistribution of pFAK-independent active α5ß1-integrin to assorted endosomes. Importantly, the development of a simultaneous multi-channel immunofluorescence approach and new algorithms for computational batch-analysis and their application to a human PDAC panel, indicated that stromal localization and levels of active SMAD2/3 and α5ß1-integrin distinguish patient-protective from patient-detrimental desmoplasia and foretell tumor recurrences, suggesting a useful new prognostic tool.


Assuntos
Fibroblastos Associados a Câncer/química , Carcinoma Ductal Pancreático/complicações , Carcinoma Ductal Pancreático/patologia , Membrana Celular/química , Fibroma Desmoplásico/complicações , Fibroma Desmoplásico/patologia , Integrina alfa5beta1/análise , Biomarcadores Tumorais/análise , Matriz Extracelular/metabolismo , Humanos , Fator de Crescimento Transformador beta/metabolismo
20.
BJU Int ; 120(2): 239-245, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28192632

RESUMO

OBJECTIVES: To assess the relationship between surgeon (SV) and hospital volume (HV) on mortality after radical cystectomy (RC). PATIENTS AND METHODS: We queried the National Cancer Database (NCDB) for adult patients undergoing RC between 2010 and 2013. We calculated average volume for each surgeon and hospital. Using propensity-scored weights for combined volume groups with a proportional hazards regression model, we compared the associations between HV and SV with 90-day survival after RC. RESULTS: A total of 19 346 RCs were performed at 927 hospitals by 2 927 surgeons in the period 2010-2013. The median (interquartile range) HV and SV were 12.3 (5.0-35.5) and 4.3 (1.3-12.3) cases, respectively. For HV, 90-day unadjusted mortality was 8.5% in centres with <5 cases/year (95% confidence interval [CI] 7.7-9.3) and 5.6% in those with >30 cases/year (95% CI 5.0-6.2). For SV, 90-day mortality was 8.1% for surgeons with <5 cases/year (95% CI 7.6-8.6) and 4.0% for those with >30 cases/year (95% CI 2.8-5.2; all P < 0.05). The 30-day mortality rate was lowest for the combined HV-SV groups with HV >30, ranging from 1.6% to 2.1%. CONCLUSIONS: In hospitals reporting to the NCDB, volume was associated with improved mortality after RC. These associations appear to be driven by hospital- rather than surgeon-level effects. An elevated SV had a beneficial effect on mortality at the highest-volume hospitals. These findings inform efforts to regionalize complex surgical care and improve quality at community and safety net hospitals.


Assuntos
Competência Clínica , Cistectomia/mortalidade , Cistectomia/estatística & dados numéricos , Hospitais com Alto Volume de Atendimentos/estatística & dados numéricos , Cirurgiões/estatística & dados numéricos , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Modelos de Riscos Proporcionais , Sistema de Registros , Adulto Jovem
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